Focused Ultrasound for Immunomodulation of the Tumor Microenvironment

Focused ultrasound (FUS) has recently emerged as a modulator of the tumor microenvironment, paving the way for FUS to become a safe yet formidable cancer treatment option. Several mechanisms have been proposed for the role of FUS in facilitating immune responses and overcoming drug delivery barriers. However, with the wide variety of FUS parameters used in diverse tumor types, it is challenging to pinpoint FUS specifications that may elicit the desired antitumor response. To clarify FUS bioeffects, we summarize four mechanisms of action, including thermal ablation, hyperthermia/thermal stress, mechanical perturbation, and histotripsy, each inducing unique vascular and immunological effects. Notable tumor responses to FUS include enhanced vascular permeability, increased T cell infiltration, and tumor growth suppression. In this review, we have categorized and reviewed recent methods of using therapeutic ultrasound to elicit an antitumor immune response with examples that reveal specific solutions and challenges in this new research area.